Citations 4
A randomized, double-blind, placebo-controlled study of losmapimod in patients with facioscapulohumeral muscular dystrophy: Results of the REACH study
Voermans, Nicol C, Statland, J., Hayward, Lawrence J. , Rosenbohm, Angela , Munain, Adolfo López de, Sacconi, Sabrina, Leung, D., Vissing, John, Schoser, Benedikt, Lochmüller, H., Bugiardini, E., Wang, Leo H. , Maggi, Lorenzo, Ragole, Thomas , Pestronk, Alan , Hamel, Johanna , Goyal, Namita A, Korngut, Lawrence, Naddaf, Elie, Harper, A., Shieh, Perry, Kornblum, Cornelia , Sansone, Valeria, Genge, A., Tasca, G., Jiang, John , Jouvin, Marie‐Hélène , Tawil, Rabi , Investigators, on behalf of the REACH, Leung, Doris G , Muelas, Nuria , Wang, Leo H , Pestronk, Alan , Goyal, Namita A , Harper, Amy , Tasca, Giorgio , Tawil, Rabi , Voermans, Nicol Cornelia , Statland, Jeffrey M., Munaín, Adolfo López de , Sacconi, Sabrina , Badrising, Umesh A. , Vissing, John , Schoser, Benedikt , Bugiardini, Enrico , Maggi, Lorenzo , Korngut, Lawrence , Naddaf, Elie , Shieh, Perry B. , Sansone, Valeria , Genge, Angela
Journal of Neuromuscular Diseases | February 6, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available
Background: Losmapimod is an orally administered small molecule and selective p38α/β mitogen-activated protein kinase (MAPK) inhibitor able to reduce aberrant expression of DUX4 in vitro and thereby potentially slowing disease progression in patients with facioscapulohumeral muscular dystrophy (FSHD). Objective: This global, randomized, placebo-controlled, double-blind phase 3 study in patients with FSHD1 and FSHD2 examined the efficacy and safety of losmapimod over a 48-week treatment period compared to placebo (NCT05397470, EUDRACT 2022-000389-16). Methods: The primary endpoint was change in quantification of reachable workspace (RWS) expressed as relative surface area (RSA). Other endpoints included measures of muscle composition (fat content and lean muscle) using magnetic resonance imaging (MRI), muscle strength using quantitative dynamometry, and quality of life measures. Results: 130 participants received losmapimod and 130 participants received placebo, with 252 participants completing the 48-week treatment period. There were no statistically significant differences between groups in change in RSA and all secondary efficacy endpoints from baseline to Week 48. Losmapimod treatment was well-tolerated, and most adverse events were mild. Conclusions: Losmapimod was generally well tolerated with a favorable safety profile at a dose of 15 mg twice daily. Although none of the efficacy endpoints were met, study design and data from the study may inform future studies of FSHD therapies.
Characterization of Factors Associated With Death in Deceased Patients With Mitochondrial Disorders
Ivaniuk, Alina , Anselm, Irina , Bowen, Aaron B. , Cohen, Bruce H. , Eminoğlu, Fatma Tuba , Estrella, Jane , Gallagher, Renata C. , Gannon, Jennifer , Gorman, Gráinne S. , Greene, Carol L. , Haas, Richard , Kapoor, Seema , Karaa, Amel , Koenig, Mary Kay , Kornblum, Cornelia , Lichter‐Konecki, Uta , Lopriore, Piervito , McFarland, Robert , Moe, Aye , Ng, Yi Shiau , Saneto, Russell P. , Scaglia, Fernando , Tarnopolsky, Mark A. , Walker, Melissa , Group, as the Hong Kong Mitochondrial Diseases Interest, Fung, Cheuk Wing , Wong, Tsz-sum, Belaramani, Kiran , Chan, Chun-kong , Chan, Wing-ki, Chan, Wai-lun Larry, Cheung, H. M. E., Cheung, Ka-yin, Chang, Richard Shek‐kwan , Cheung, Sing-ngai, Cheung, Tsz-Fung, Cheung, Yuk-fai, Chong, Shuk-ching Josephine, Chow, Chi-kwan Jasmine , Fan, Florence , Fok, Wai-ming Joshua , Fung, Tsui-hang Sharon , Hui, Kwok-fai, Hui, Ting-hin, Ko, Chun Hung, Kwan, Min-chung, Kwok, Anne Mei Kwun , Kwok, Sung-shing Jeffrey, Lai, Moon-sing, Lam, Yau-on, Lam, Ching‐Wan , Lau, Ming-chung, Law, Hiu-Fung, Lee, Wing‐Cheong , Leung, Kin-hang, Leung, Kit-yan, Li, Siu-hung, Ling, Tsz-ki, Liu, Kam Tim , Lui, Colin H. T., Luk, Ching-on, Luk, Ho‐Ming , Ma, Che-Kwan, Ma, Karen , Ma, Kam-hung , Mew, Yuen-ni, Mo, Alex, Hg, Sui-Fun, Poon, Grace Wing-kit , Sheng, Bun , Szeto, Cheuk-ling Charing, Tai, Shuk‐Mui, Tang, Jing-Liang, Tse, Choi-ting Alan , Tsung, Li-yan Lilian, Wong, Ho-ming June, Wong, Wing-yin Winnie, Wong, Kwok-kui, Wong, Suet-na Sheila , Wong, Chun-nei Virginia, Wong, Wai-shan Sammy, Wong, Chi-kin Felix, Wu, Shun-Ping, Wu, Hiu-fung Jerome , Yau, Man-Mut, Yau, Eric Kin Cheong , Yeung, Wai Lan , Yeung, Hon‐Ming Jonas , Yip, Kin-keung Edwin, Young, Pui-hong Terence, Yuan, Gao , Yuen, Yuet‐Ping , Yuen, Chi-lap, Anselm, Irina A , Bowen, Aaron , Ganetzky, Rebecca D , Gannon, Jennifer , Gorman, Grainne S , Greene, Carol , Gropman, Andrea L , Haas, Richard H , Hirano, Michio , Kapoor, Seema , Karaa, Amel , Koenig, Mary Kay , Kornblum, Cornelia , Kose, Engin , Larson, Austin A , Lichter-Konecki, Uta , Lopriore, Piervito , Mancuso, Michelangelo , McFarland, Robert , Moe, Aye Myat , Ng, Yi Shiau , Saneto, Russell P , Scaglia, Fernando , Sue, Carolyn M , Tarnopolsky, Mark , Walker, Melissa A , Parikh, Sumit , Cheuk-Wing, Fung , Wong, Tsz-Sum , Belaramani, Kiran , Chan, Chun-Kong , Chan, Wing-Ki , Chan, Wai-Lun Larry , Cheung, Hon-Wing , Cheung, Ka-Yin , Chang, Shek-Kwan , Cheung, Sing-Ngai , Cheung, Tsz-Fung , Cheung, Yuk-Fai , Chow, Chi-Kwan Jasmine , Chung, Hon-Yin B , Fan, Sin-Ying Florence , Fok, Wai-Ming Joshua , Fung, Tsui-Hang Sharon , Hui, Kwok-Fai , Hui, Ting-Hin , Hui, Joannie , Ko, Chun Hung , Kwan, Min-Chung , Kwok, Mei-Kwan Anne , Kwok, Sung-Shing Jeffrey , Lai, Moon-Sing , Lam, Yau-On , Lam, Ching-Wan , Lau, Ming-Chung , Law, Chun-Yiu Eric , Law, Hiu-Fung , Lee, Wing-Cheong , Leung, Kin-Hang , Leung, Kit-Yan , Li, Siu-Hung , Liu, Kam-Tim Timothy , Lo, Fai-Man , Lui, Colin , Luk, Ho-Ming , Ma, Che-Kwan , Ma, Karen , Ma, Kam-Hung , Mo, Alex , Hg, Sui-Fun , Poon, Wing-Kit Grace , Sheng, Bun , Tse, Choi-Ting Alan , Wong, Ho-Ming June , Wong, Wing-Yin Winnie , Wong, Kwok-Kui , Wong, Suet-Na Sheila , Wong, Chun-Nei Virginia , Wong, Wai-Shan Sammy , Wu, Hiu-Fung Jerome , Yau, Kin-Cheong Eric , Yeung, Wai-Lan , Yeung, Hon-Ming Jonas , Yip, Kin-Keung Edwin , Young, Pui-Hong Terence , Yuan, Gao , Yuen, Yuet-Ping Liz , Ivaniuk, Alina , Cohen, Bruce H , Ganetzky, Rebecca , Larson, Austin , Morava, Éva , Sue, Carolyn M. , Parikh, Sumit , Group, as the Hong Kong Mitochondrial Diseases Interest, Fong, Ka-Wing, Lee, Han‐Chih Hencher , Tang, Jing-Liang, Wu, Hui-Jun
Neurology | January 30, 2025 | Volume: 104 | Issue: 4 | Pages: No page available
A new muscle glycogen storage disease associated with Glycogenin-1 deficiency (S34.002)
Hedberg‐Oldfors, Carola , Hernández‐Laín, Aurelio , Viennet, G., Michel, Fabrice , Ackman, Hasan, Kornblum, Cornelia , Romero, Norma B., Engel, Andrew, DiMauro, Salvatore, Malfatti, Edoardo , Nilsson, Johanna E. , Domínguez‐González, Cristina , Michel, Fabrice, Bergh, Peter Y. K. Van den , Romero, Norma B. , Oldfors, Anders
Neurology | December 6, 2023 | Volume: 84 | Issue: 14_supplement | Pages: No page available
A new muscle glycogen storage disease associated with glycogenin‐1 deficiency
Hedberg‐Oldfors, Carola , Hernández‐Laín, Aurelio , Michel, Fabrice , Domínguez‐González, Cristina , Viennet, G., Akman, Hasan O. , Kornblum, Cornelia , Romero, Norma B., DiMauro, Salvatore, Oldfors, Anders , Malfatti, Edoardo , Nilsson, Johanna E. , Bergh, Peter Y. K. Van den , Engel, Andrew G.
Annals of Neurology | October 1, 2014 | Volume: 76 | Issue: 6 | Pages: 891-898
We describe a slowly progressive myopathy in 7 unrelated adult patients with storage of polyglucosan in muscle fibers. Genetic investigation revealed homozygous or compound heterozygous deleterious variants in the glycogenin‐1 gene (GYG1). Most patients showed depletion of glycogenin‐1 in skeletal muscle, whereas 1 showed presence of glycogenin‐1 lacking the C‐terminal that normally binds glycogen synthase. Our results indicate that either depletion of glycogenin‐1 or impaired interaction with glycogen synthase underlies this new form of glycogen storage disease that differs from a previously reported patient with GYG1 mutations who showed profound glycogen depletion in skeletal muscle and accumulation of glycogenin‐1. Ann Neurol 2014;76:891–898